Contraceptive methods for men are considered an essential component of world-wide reproductive health (Nieschlag and Behre; Testosterone: action, deficiency, substitution, 1998, Springer, Berlin, p 514). Hormonal methods of male contraception offer the advantages of high-reversibility and efficacy. In hormonal male contraception, the suppression of spermatogenesis is sought through the suppression of the gonadotropins leuteinizing hormone (LH) and follicle stimulating hormone (FSH) to undetectable levels within the endocrine feedback mechanism operating between the pituitary gland and the hypothalamus. Disadvantageously, suppression of these gonadotropins also induces symptoms related to androgen deficiency (Nieschlag and Behre; 1998, pp 513–528).
Male contraceptive methods seek to suppress FSH and LH, resulting in a depletion of intratesticular testosterone and cessation of spermatogenesis, whilst substituting peripheral testosterone with another androgen. This androgen has typically been testosterone itself and serves the endocrine androgenic role of testosterone such as to maintain libido, male sex characteristics, protein anabolism, hematopoesis and others. In short, the objective is to deplete the testes of testosterone whilst maintaining levels in the general circulation.
The suppression of spermatogenesis by administration of testosterones alone have been ineffective in inducing azoospermia. The administration of gonadotropin releasing hormone antagonists (GnRH antagonists) has circumvented part of the problem with the administration of high levels of testosterone alone but GnRH antagonists are unattractive for clinical use in their current preparations and are generally expensive to prepare.
The use of either the progestins cyproterone acetate or levonorgestrel were either ineffective in the suppression of spermatogenesis or, in higher doses, led to significant decreases in red blood cell count (Merrigiola et al, 1998; Merrigiola et al, 1997; Merrigiola et al, 1996; Bebb et al, 1996).
The use of a mixture of two compounds, one an androgen and another an estrogen, in combination is disclosed in U.S. Pat. No. 4,210,644.
A method towards the inhibition of spermatogenesis in men by administering testosterone percutaneously or orally and the progestin norethisterone acetate orally has been disclosed (Guerin and Rollet, 1988). However, high doses relative to amounts required by the present invention of each component were required to achieve azoospermia.
Thus, effective and efficient methods of male contraceptive by use of a male contraceptive formulation are not currently available.